Slide 1: Objective clinical response by KRAS mutation-specific TCR-T cell therapy in previously treated advanced NSCLC
Exhibit 99.1 Objective clinical response by KRAS mutation- specific TCR-T cell therapy in previously treated advanced non-small cell lung cancer Marcelo V. Negrao, MD Assistant Professor Department of Thoracic / Head and Neck Medical Oncology University of Texas MD Anderson Cancer Center
Slide 2: Forward Looking Statements Disclaimer
Forward Looking Statements Disclaimer This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as “m
Slide 3: Adoptive T-Cell Therapy has Activity in Solid Tumors
Adoptive T-Cell Therapy has Activity in Solid Tumors 1 ▪ Melanoma: expanded TILs ORR 34-56% 2 ▪ HPV+ SCC: HPV-TIL ORR 18-28% 3 ▪ MBC: enriched TILs ORR 67% 4 ▪ NSCLC: expanded TILs response rate 46% 5 ▪ CRC: TIL produced durable response 6 ▪ PDAC: durable response and persistence of TCR-T cells 1. R
Slide 4: KRAS Mutations are Logical Targets for T-Cell Therapy due to High Prevalence in Epithelial Solid Tumors
KR AS Mutations are Logical Targets for T-Cell Therapy due to High Prevalence in Epithelial Solid Tumors Lung CholangioCA Adenocarcinoma Key: G12C Pancreatic G12D Ovarian Adenocarcinoma G12V Other KRAS Mut. Wild Type KRAS Colorectal Endometrial Adenocarcinoma 1 Judd et al. Mol Cancer Ther. 2021 2 Ca
Slide 5: Phase I/II Trial to Determine the Safety and Efficacy of Non-viral TCR-T Cell Therapy for Treatment of Solid Tumors
Phase I/II Trial to Determine the Safety and Efficacy of Non-viral TCR-T Cell Therapy for Treatment of Solid Tumors ▪ ClinicalTrials.gov: NCT05194735 ▪ Solid tumors failed 1+ lines of therapy ▪ HLA + cancer gene mutation match for TCR library ▪ Accelerated dose escalation: BOIN design 9 9 9 ▪ 3 dose
Slide 6: TCR Library Designed to Target Tumor Neoantigens Derived from Hotspot Mutations
TCR Library Designed to Target Tumor Neoantigens Derived from Hotspot Mutations ▪ Common cancer gene mutations: KRAS, TP53, EGFR ▪ Common HLAs: A*02:01 / A*11:01 ▪ Library expansion: identification of novel anti-tumor reactive TCRs ▪ More TCRs = more eligible patients Genes Mutations HLA Types G1
Slide 7: Non-viral Sleeping Beauty System Designed to Enable Manufacture of TCR-T Cells without Complex Gene Editing
Non-viral Sleeping Beauty System Designed to Enable Manufacture of TCR-T Cells without Complex Gene Editing ▪ Efficient integration without the complexity of gene editing or viral approaches ▪ Rapid, cost-effective manufacturing ▪ Accommodates large transgene size ▪ Expected to be scalable for clini
Slide 8: Patient 1: Immune Checkpoint Inhibitor and Chemotherapy Refractory KRAS G12D NSCLC
Patient 1: Immune Checkpoint Inhibitor and Chemotherapy Refractory KRAS G12D NSCLC ▪ 34yo, female, never smoker, lung adenocarcinoma ▪ Left lower lobectomy and adjuvant cisplatin and vinorelbine x 4 cycles ▪ Disease recurrence in the lungs 4 months after adjuvant treatment ▪ KRAS G12D mutation posit
Slide 9: Patient 1: Immune Checkpoint Inhibitor and Chemotherapy Refractory KRAS G12D NSCLC (continued)
Patient 1: Immune Checkpoint Inhibitor and Chemotherapy Refractory KRAS G12D NSCLC ▪ Durvalumab + CTLA4 inhibitor + MEK inhibitor on trial – discontinued due to progression ▪ SHP2 inhibitor single-agent on trial – discontinued due to progression ▪ Library TCR match: KRAS G12D HLA-A*11:01
Slide 10: TCR-T Cells Observed to Specifically Recognize and Kill Targets Expressing KRAS G12D
TCR-T Cells Observed to Specifically Recognize and Kill Targets Expressing KRAS G12D Presented by HLA-A*11:01 Neoantigen-Specific Activation Effector Cytokine Secretion Tumor Killing ✱✱✱ 100 100 80 80 60 60 Mutant KRAS G12D Mutant KRAS G12D 40 40 Wild Type KRAS 20 20 Wild Type KRAS 0 0 [peptide], μg
Slide 11: High TCR Expression and Purity of TCR-T Cells Manufactured with Sleeping Beauty Transposition
High TCR Expression and Purity of TCR-T Cells Manufactured with Sleeping Beauty Transposition TCR-T Infusion Product (Patient 1: KRAS G12D/HLA-A*11:01) Result Viability 95.1% 9 Total TCR-T Cells 9x10 CD3+ Purity 99.7% TCR+ 95.2% CD4:CD8 Ratio 0.32 VCN 5
Slide 12: Had Manageable Safety Events During Lymphodepletion Chemotherapy
Patient 1 Had Manageable Safety Events During Lymphodepletion Chemotherapy Chest Pain - Small R pneumothorax Related to pre-treatment biopsy Hospital Admission Lymphodepletion Days of Administration Dose Drug (LD) Prior to TCR-T Infusion Cyclophosphasmide 60 mg/kg -8, -7 2 Fludarabine 25 mg/m -8, -7
Slide 13: Had Manageable Safety Events After Lymphodepletion Chemotherapy and TCR-T cell infusion
Patient 1 Had Manageable Safety Events After Lymphodepletion Chemotherapy and TCR-T cell infusion CRS Gr2 – 6hrs post-TCR-T infusion Hypoxia / Tachycardia / Fever O2 nasal cannula 2L / anti-pyretics / IV fluids / self-limited Hospital Discharge TCR-T Cell Day 11 Infusion TCR-T Cell Target Dose 9 9x1
Slide 14: Had Transient Elevation in Inflammatory Cytokines Associated with Onset and Resolution of CRS
Patient 1 Had Transient Elevation in Inflammatory Cytokines Associated with Onset and Resolution of CRS CRS = Cytokine Release Syndrome
Slide 15: Patient 1: Complete Resolution of Right Lower Lobe Lesion
Patient 1: Complete Resolution of Right Lower Lobe Lesion Insert Image Here Insert Image Here Insert Image Here 0 6 12 Baseline Week 6 Week 12 1.3 cm 0.0 cm 0.0 cm
Slide 16: Patient 1: Reduction of Right Upper Lobe Lesion
Patient 1: Reduction of Right Upper Lobe Lesion 0 6 12 Baseline Week 6 Week 12 1.3 cm 1.1 cm 1.0 cm
Slide 17: Patient 1: Reduction of Right Hilar Lymphadenopathy and Non-Measurable Right Upper Lobe Lesion
Patient 1: Reduction of Right Hilar Lymphadenopathy and of Non-Measurable Right Upper Lobe Lesion 0 6 12 Baseline Week 6 Week 12 1.5 cm 1.1 cm 1.0 cm
Slide 18: Had a Confirmed Objective Partial Response at Week 12
Patient 1 Had a Confirmed Objective Partial Response at Week 12 Baseline Week 6 Week 12 Target Lesions (mm) #1: Right lower lobe 13 0 0 #2: Right upper lobe 13 11 10 #3: Right hilar lymph node 15 11 10 Sum of Diameters (mm) 41 22 20 Percent Change -46.30% -51.20% Non-Target Lesions Bilateral lung no
Slide 19: TCR-T Cells Exhibited Rapid Expansion and Ongoing Persistence at Week 12
Patient 1 TCR-T Cells Exhibited Rapid Expansion and Ongoing Persistence at Week 12 Circulating TCR-T Cells Day 4 Week 12 1250 1000 TCR-T Cells/uL 1,038 134 5 4 750 TCR-T Copies/μg 5x10 2.5x10 500 % TCR-T+ of CD3+ 98.4% 22.5% 250 0 0 2 4 6 8 12 Weeks Post-Infusion Baseline Day 4 Week 4 Week 6 Week 12
Slide 20: Patient Serum Interferon-γ was Associated with TCR-T Cell Expansion and Persistence
TCR-T Cells / μL Blood Patient 1 Serum Interferon-γ was Associated with TCR-T Cell Expansion and Persistence 750 1250 TCR-T Cells CRS IFN-γ 600 1000 450 750 300 500 150 250 0 0 0 1 2 4 6 8 10 12 Weeks Post-Infusion CRS = Cytokine Release Syndrome IFN-γ Serum Conc. [pg/mL]
Slide 21: Patient 2: Previously Treated Advanced CRC
Patient 2: Previously Treated Advanced CRC ▪ 54yo, female, metastatic colorectal cancer ▪ Progressed on one prior line of therapy (FOLFIRI+Bevacizumab) ▪ Library TCR match: TP53 R175H HLA-A*02:01 9 ▪ TCR-T infusion of 64x10 TCR-T cells - Dose Level 2
Slide 22: Had Manageable Safety Events After TCR-T Cell Infusion
Patient 2 Had Manageable Safety Events After TCR-T Cell Infusion CRS Gr3 Fever / Hypotension / Tachycardia / Hypoxia O2 HFNC 40L 50% and Tocilizumab TCR-T Cell Target Dose TCR-T Cell 9 Hospital 64x10 TCR+ T Cells TP53 R175H/HLA-A*02:01 Infusion Admission (Dose Level 2) Lymphodepletion Days of Admini
Slide 23: Achieved Best Overall Response of Stable Disease
Patient 2 Achieved Best Overall Response of Stable Disease Baseline Week 6 Week 12 Target Lesions #1: Pelvic Mass (mm) 65 48 67 #2: Retroperitoneal Lymph Node (mm) 27 30 28 Sum of Diameters (mm) 92 78 95 Percent Change -15.20% 21.80% New Lesion No Liver / Lung Stable Progressive Overall Response Dis
Slide 24: Treatment of Patients was Tolerable with a Manageable Safety Profile
Treatment of Patients 1 and 2 was Tolerable with a Manageable Safety Profile ▪ Cytopenias expected with lymphodepletion regimen were observed in both patients ▪ Manageable CRS observed • No mechanical ventilation • No ICU admission • No vasopressors ▪ No TCR-T cell related DLTs ▪ No ICANS DLT = Dose
Slide 25: Confirmed Objective Response in Immune Checkpoint Inhibitor Refractory KRAS G12D-mutant NSCLC Treated with TCR-T Cells
Confirmed Objective Response in Immune Checkpoint Inhibitor Refractory KRAS G12D-mutant NSCLC Treated with TCR-T Cells ▪ Immune checkpoint inhibitor refractory advanced NSCLC patient treated with TCR-T cells has confirmed partial response ▪ First confirmed response to TCR-T cell therapy targeting ho
Slide 26: Sleeping Beauty System is a Promising Platform for TCR-T Cell Therapy and Trial Enrollment is Ongoing
S leeping Beauty System is a Promising Platform for TCR-T Cell Therapy and Trial Enrollment is Ongoing ▪ First report of successful TCR-T cell therapy using non-viral Sleeping Beauty system for solid tumors ▪ Proof of concept of manufacturing TCR-T targeting KRAS and TP53 ▪ Ongoing persistence of TC
Slide 27: Acknowledgements
Acknowledgements MDACC Study Team Alaunos Therapeutics Marcelo V. Negrao Nathan Demars Maria Pia Morelli Jaymes Holland Partow Kebriaei Matthew R. Collinson-Pautz Amir Jazaeri Frances Adeyemi Benny Johnson Amanda Montoya Thank you to all Shubham Pant Victor Carpio the patients and Laura Henderson La